Hypertension remains a major public health problem despite advances in treatment strategies. Arterial stiffness increases with advancing age and is thought to contribute to the increase prevalence of isolated systolic hypertension (ISH) in older adults. With the inevitable increase in older adults in the population, increases in numbers of older hypertensives can be expected. New/alternative interventional strategies to reduce systolic blood pressure (SBP) require investigation. The specific aims of this proposal are to determine: 1) if 8 weeks of vitamin E therapy will reduce systolic blood pressure (SBP) in older adults with ISH; 2) if 8 weeks of vitamin E therapy will reduce arterial stiffness in older adults with ISH; and, 3) if 8 weeks of vitamin E therapy will improve endothelium-dependent vasodilation in older adults with ISH. Our experimental hypothesis is that antioxidant therapy (Vitamin E) will improve endothelium-dependent vasodilation and arterial stiffness, thus reducing SBP in the older adult. As a consequence, aortic input impedance will be reduced, which will in turn decreased cardiac work. Forty, 6-80 year old subjects with ISH will be recruited. A randomized double-blind, placebo-controlled design will be employed to achieve the specific aims. Subjects will be randomized into a placebo or treatment (vitamin E, 400 IU/d) group. Following baseline measurements, subjects will take vitamin E or placebo each day for 8 weeks, with measurements repeated at 4 and 8 weeks. Measurements will include: blood pressure via standard auscultatory techniques; global and regional arterial stiffness via ultrasound [of the hear, brachial artery, and carotid artery], applanation tonometry, and pulse wave velocities; and, endothelium-dependent vasodilatory capacity via intra-arterial infusions of acetylcholine and nitroprusside, as well as, post-ischemic, flow-dependent vasodilatory capacity of the brachial artery. Plasma nitrate will be determined as an index of nitric oxide production. This study will provide new and clinically relevant information on the role of antioxidant therapy in the treatment of hypertension in middle-aged and older adults.